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Triptolide suppresses interleukin-1ß-induced human ß-defensin-2 mRNA expression through inhibition of transcriptional activation of NF-κB in A549 cells

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Author(s)
BYEONG-CHURL JANGKI-JO LIMIN-HAK CHOIMIN-HO SUHJONG-GU PARKKYO-CHUL MUNJAE-HOON BAEDONG-HOON SHINSEONG-IL SUH
Keimyung Author(s)
Jang, Byeong ChurlPark, Jong GuSuh, Min HoSuh, Seong IlMun, Kyo CheolBae, Jae HoonShin, Dong Hoon
Department
Dept. of Molecular Medicine (분자의학)
Dept. of Microbiology (미생물학)
Dept. of Biochemistry (생화학)
Dept. of Physiology (생리학)
Dept. of Preventive Medicine (예방의학)
Institute for Medical Science (의과학연구소)
Journal Title
International Journal of Molecular Medicine
Issued Date
2007
Volume
19
Issue
5
Abstract
. The immunosuppressive effect of triptolide has been
associated with suppression of T-cell activation. However, the
immunosuppressive effects of triptolide on innate immunity
in the epithelial barrier remain to be elucidated. Human ßdefensin
(HBD)-2 is an inducible antimicrobial peptide and
plays an important role in the innate immunity. We have
previously demonstrated that IL-1ß induced HBD-2 mRNA
expression in A549 cells through activation of nuclear factor-
κB (NF-κB) transcriptional factor as well as p38 mitogenactivated
protein kinase (MAPK), c-Jun N-terminal kinase
(JNK), or phosphatidylinositol-3-kinase (PI3K). In this study,
we investigated effects of triptolide on IL-1ß-induced HBD-2
mRNA expression in A549 cells. Triptolide inhibited IL-1ßinduced
HBD-2 mRNA expression in a dose-dependent
manner. Addition of triptolide did not suppress activation of
p38 MAPK, JNK, or PI3K in response to IL-1ß. Triptolide
inhibited IL-1ß-induced MAPK phosphatase-1 expression at
the transcriptional level and resulted in sustained phosphorylation
of JNK or p38 MAPK, explaining the little effect of
triptolide on IL-1ß-induced phosphorylation of these kinases.
Although triptolide partially suppressed IL-1ß-mediated
degradation of IκB-· and nuclear translocation of p65 NF-κB,
triptolide potently inhibited NF-κB promoter-driven luciferase
activity in A549 cells. These results collectively suggest that
the inhibitory effect of triptolide on IL-1ß-induced HBD-2
mRNA expression in A549 cells seems to be at least in part
mediated through nuclear inhibition of NF-κB transcriptional
activity, but not inhibition of p38 MAPK, JNK, or PI3K. This
inhibition may explain the ability of triptolide to diminish
innate immune response.
Keimyung Author(s)(Kor)
장병철
박종구
서민호
서성일
문교철
배재훈
신동훈
Publisher
School of Medicine
Citation
BYEONG-CHURL JANG et al. (2007). Triptolide suppresses interleukin-1ß-induced human
ß-defensin-2 mRNA expression through inhibition of
transcriptional activation of NF-κB in A549 cells. International Journal of Molecular Medicine, 19(5), 757–763. doi: 10.3892/ijmm.19.5.757
Type
Article
ISSN
1107-3756
Source
https://www.spandidos-publications.com/ijmm/19/5/757?text=abstract
DOI
10.3892/ijmm.19.5.757
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/35921
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Biochemistry (생화학)
1. School of Medicine (의과대학) > Dept. of Microbiology (미생물학)
1. School of Medicine (의과대학) > Dept. of Molecular Medicine (분자의학)
1. School of Medicine (의과대학) > Dept. of Physiology (생리학)
1. School of Medicine (의과대학) > Dept. of Preventive Medicine (예방의학)
3. Research Institutues (연구소) > Institute for Medical Science (의과학연구소)
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